During the last decennium, uridine, choline and omega-3 fatty acids such as DHA have attracted attention as active components in treating cognitive dysfunction and age-associated memory impairment (AAMI), see e.g. WO2007/089703 (Massachusetts Institute of Technology) and WO 2009/002165 (N.V. Nutricia). These compounds are rate-limiting precursors for membrane phosphatide synthesis. According to the above applications, by improving the membrane phosphatide synthesis, it is believed to improve cognitive or memory function. The effects on membrane phospholipids have been associated with enhancement in specific pre- and post-synaptic proteins.
WO 2013/066165 and WO 2013/066167 (N.V. Nutricia) disclose a product comprising (i) one or more of uridine and cytidine, or salts, phosphates, acyl derivatives or esters thereof, and (ii) a lipid fraction comprising at least one of docosahexaenoic acid 5 (22:6; DHA), eicosapentaenoic acid (20:5; EPA) and docosapentaenoic acid (22:5; DPA), or esters thereof, recognition and executive functions like speed of information processing, cognitive and mental flexibility, attention, scanning, and cognitive set shifting can be improved, in particular in a Alzheimer's or dementia patient. WO 2012/125020 discloses a similar product for use in the prevention or treatment of neurotrauma, traumatic brain injury, cerebral palsy and spinal cord injury.
In the art, focus of attention has been on subjects suffering from or at immediate risk of developing dementia and/or Alzheimer's Disease [AD]. As for instance addressed in EP 1.800.675 [N.V. Nutricia], dementia and AD are associated with shrinkage of the brain volume and in particular of the volume of the white matter. Neurodegeneration associated with the above neurodegenerative disorders typically results in death of neurons and a generalized form of cerebral atropy and volume loss, while damaged neurons, including their myelinated axons will be removed from the brain. Such pathology is therefore characterized by a generalized localization and a generalized loss in volume or mass (brain “shrinkage”). The neurodegeneration is commonly associated with the formation of protein agglomerates, which manifest themselves as amyloid plaques or Lewy bodies. When applying brain imaging of such affected brains one typically observes less white matter but also larger ventricles and morphological changes in the grey matter, and optical representations of the protein agglomerates. Volume loss of white matter is recognized to be a pathology that differs from the rather localized hyperintensities around the lateral ventricles in brain, which are frequently observed in elderly, even when they do not experience neurodegeneration.
Multiple sclerosis is also considered to affect white matter, due to a fierce reaction of the immune system on the myelin sheaths of neurons, either present centrally or in peripheral tissues. Such white matter pathology is characterized by a general nature in localization and a consistent decrease in quality of the myelin sheath during the progression of the pathology, caused by a progressing decrease in thickness of the myelin sheaths. The loss of quality can be assessed by measuring for example the speed of transmission of nerve signals. Again, it is pathologically distinct from WMH, Leukoaraiosis or periventricular white matter disease.
There remains a need to target age-associated white matter lesions, white matter hyperintensities (WMH), Leukoaraiosis or periventricular white matter disease in the art.